PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 10751024

Cationic polymer based gene delivery systems.

S C De Smedt·J Demeester·W E Hennink
View original source ↗Export metadata ↓

Abstract

Gene transfer to humans requires carriers for the plasmid DNA which can efficiently and safely carry the gene into the nucleus of the desired cells. A series of chemically different cationic polymers are currently being investigated for these purposes. Although many cationic polymers indeed condense DNA spontaneously, which is a requirement for gene transfer in most types of cells, the physicochemical and biopharmaceutical behavior of the current generation of polyplexes severely limits an efficient gene transfer in vitro and especially in vivo. This paper summarizes recent physicochemical and biological information on polyplexes and aims to provide new insights with respect to this type of gene delivery system. Firstly, the chemical structure of frequently studied cationic polymers is represented. Secondly, the parameters influencing condensation of DNA by cationic polymers are described. Thirdly, the surface properties, solubility, aggregration behavior, degradation and dissociation of polyplexes are considered. The review ends by describing the in vitro and in vivo gene transfection behavior of polyplexes.

Explore related subjects

CationsDrug Delivery SystemsGenetic TherapyHumansPlasmidsPolymersJournal ArticleResearch Support, Non-U.S. Gov'tReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

S C De Smedt, J Demeester, W E Hennink. 2000. Cationic polymer based gene delivery systems.. https://doi.org/10.1023/a%3A1007548826495

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2001

Selective interactions of cationic porphyrins with G-quadruplex structures.

G-quadruplex DNA presents a potential target for the design and development of novel anticancer drugs. Because G-quadruplex DNA exhibits structural polymorphism, different G-quadruplex typologies may be associated with different cellular processes. Therefore, to achieve therapeutic selectivity using G-quadruplexes as targets for drug design, it will be necessary to differentiate between different types of G-quadruplexes using G-quadruplex-interactive agents. In this study, we compare the interactions of three cationic porphyrins, TMPyP2, TMPyP3, and TMPyP4, with parallel and antiparallel types of G-quadruplexes using gel mobility shift experiments and a helicase assay. Gel mobility shift experiments indicate that TMPyP3 specifically promotes the formation of parallel G-quadruplex structures. A G-quadruplex helicase unwinding assay reveals that the three porphyrins vary dramatically in their abilities to prevent the unwinding of both the parallel tetrameric G-quadruplex and the antiparallel hairpin dimer G-quadruplex DNA by yeast Sgs1 helicase (Sgs1p). For the parallel G-quadruplex, TMPyP3 has the strongest inhibitory effect on Sgs1p, followed by TMPyP4, but the reverse is true for the antiparallel G-quadruplex. TMPyP2 does not appear to have any effect on the helicase-catalyzed unwinding of either type of G-quadruplex. Photocleavage experiments were carried out to investigate the binding modes of all three porphyrins with parallel G-quadruplexes. The results reveal that TMPyP3 and TMPyP4 appear to bind to parallel G-quadruplex structures through external stacking at the ends rather than through intercalation between the G-tetrads. Since intercalation between G-tetrads has been previously proposed as an alternative binding mode for TMPyP4 to G-quadruplexes, this mode of binding, versus that determined by a photocleavage assay described here (external stacking), was subjected to molecular dynamics calculations to identify the relative stabilities of the complexes and the factors that contribute to these differences. The DeltaG(o) for the external binding mode was found to be driven by DeltaH(o) with a small unfavorable TDeltaS(o) term. The DeltaG(o) for the intercalation binding model was driven by a large TDeltaS(o) term and complemented by a small DeltaH(o) term. One of the main stabilizing components of the external binding model is the energy of solvation, which favors the external model over the intercalation model by -67.94 kcal/mol. Finally, we propose that intercalative binding, although less favored than external binding, may occur, but because of the nature of the intercalative binding, it is invisible to the photocleavage assay. This study provides the first experimental insight into how selectivity might be achieved for different G-quadruplexes by using structural variants within a single group of G-quadruplex-interactive drugs.

Cations↗
PubMed2001

Microemulsion polymerization of styrene in the presence of a cationic emulsifier.

The principal subject discussed in the current paper is the radical polymerization of styrene in the three- and four component microemulsions stabilized by a cationic emulsifier. Polymerization in the o/w microemulsion is a new polymerization technique which allows to prepare the polymer latexes with the very high particle interface area and narrow particle size distribution. Polymers formed are very large with a very broad molecular weight distribution. In emulsion and microemulsion polymerizations, the reaction takes place in a large number of isolated loci dispersed in the continuous aqueous phase. However, in spite of the similarities between emulsion and microemulsion polymerization, there are large differences caused by the much larger amount of emulsifier in the latter process. In the emulsion polymerization there are three rate intervals. In the microemulsion polymerization only two reaction rate intervals are commonly detected: first, the polymerization rate increases rapidly with the reaction time and then decreases steadily. Essential features of microemulsion polymerization are as follows: (1) polymerization proceeds under non-stationary state conditions; (2) size and particle concentration increases throughout the course of polymerization; (3) chain-transfer to monomer/exit of transferred monomeric radical/radical re-entry events are operative; and (4) molecular weight is independent of conversion and distribution of resulting polymer is very broad. The number of microdroplets or monomer-starved micelles at higher conversion is high and they persist throughout the reaction. The high emulsifier/water ratio ensures that the emulsifier is undissociated and can penetrate into the microdroplets. The presence of a large amount of emulsifier strongly influences the reaction kinetics and the particle nucleation. The mixed mode particle nucleation is assumed to govern the polymerization process. At low emulsifier concentration the micellar nucleation is dominant while at a high emulsifier concentration the interaction-like homogeneous nucleation is operative. Furthermore, the paper is focused on the initiation and nucleation mechanisms, location of initiation locus, and growth and deactivation of latex particles. Furthermore, the relationship between kinetic and molecular weight parameters of the microemulsion polymerization process and colloidal (water/particle interface) parameters is discussed. In particular, we follow the effect of initiator and emulsifier type and concentration on the polymerization process. Besides, the effects of monomer concentration and additives are also evaluated.

Cations↗